丹参对马兜铃酸肾损害大鼠肾组织病理学改变及ACE、ACE2表达的影响

目的：观察丹参对马兜铃酸诱导的大鼠肾组织病理改变、血管紧张素转化酶（ACE）7L其同源物AC1、2以及细胞因子表达的影响。方法：建立马兜铃酸肾损害大鼠模型，并灌服不同剂量丹参水溶液（5、10、15g·kg^-1·d^-1），于实验第12、16、20、24周留取肾组织标本，HE、P／kS、Masson观察肾组织病理改变，免疫印迹检测肾组织ACE、ACE2的蛋白表达量，RT—PCR检测AngⅡ、TGF—β1、PAI-1mRNA水平。结果：第12周开始，模型大鼠出现肾小管结构损伤，表现为刷状缘消失、细胞空泡变性、脱落，并出现裸膜，伴炎细胞浸润，实验后期出现局部动脉管壁增厚及轻度纤维化表现。模型大鼠肾组织ACE的表达升高，并随实验进展而明显；第16周开始艘的表达降低。AngⅡ、TGF—β1、PAI-1mRNA表达上调，以AngⅡ mRNA上调明显。丹参干预后肾组织病变有所减轻，未出现纤维化表现；丹参可降低肾组织ACE的表达，并下调AngⅡ mRNA水平。结论：丹参可能通过降低ACE的表达、促进ACE2的合成，抑制了AngⅡ的活性，并下调TGF-β1、PAI-1的过高表达，从而减轻马兜铃酸诱导的肾小管间质病变的发生发展。

Effect of Salvia Miltiorrhiza on Renal Pathological Change and Expression of ACE and ACE2 in Rats with Aristolochic Acid Induced Nephropathy

To investigate the effect of Salvia miltiorrhiza（SM） on the renal lesion and the expressions of ACE, ACE2 and Cytokines in rats of aristolochic acid nephropathy（AAN）. Methods： Wister rats were given the extracta of Caulis Aristolochiae Manshuriensis to establish AAN model, and then administrated SM 5,10,15 g·kg^- 1. d^- 1 resepectively. The change of renal pathology was observed through the staining of HE,PAS and Masson. Western blot was used to analyze the expression of ACE and ACE2,and RT- PCR was used to detect the levels of cytokine mRNA at the end of the 12th, 16th,20th,and 24th week. Resuits：In the renal tubular in AAN rats, such as disappearance of brush border, cells degeneration and baring of basement membrane were observed, which were followed with local artery wall thickening and mild fibrosis along as the experiment progressed. The expression of ACE increased and that of ACE2 decreased,and cytokines mRNA was upregulated correspondingly. SM could improve the abnormal change. Conclusion： SM could ameliorate the renal lesion in rats of AAN by reducing the expression of ACE and increasing the ACE2 to inhibit the Ang Ⅱ activity and also reducing the levels of TGF - βa mRNA and PAI- 1 mRNA.